Novel Antibiotics from Unculturable Actinomycetes The threat of bioterrorism requires novel effective countermeasures against CDC Category A agents. The broad objective of this project is to develop novel therapeutics against these agents by accessing the largest unexplored reservoir of biological and chemical diversity on our planet, "uncultivable" microorganisms. We have developed fundamentally novel cultivation approaches that provide unique access to these microorganisms (T.Kaeberlein, K.Lewis, and S.Epstein (2002) Science 296:1127-1129). These approaches are based on growing "uncultivables" in their natural environment, and subsequent domestication in the laboratory. In this research, we focus on one of the most promising groups of microorganisms, "uncultivable" Actinomycetes. We have been using our proprietary cultivation methodology to grow, isolate, and domesticate a large collection of novel Actinomycetes from various environments, including several types of soils and aquatic sediments. Our principal objective is to screen a library of novel isolates of Actinomycetes for activity against Bacillus anthracis, followed by validation and dereplication of novel antimicrobial compounds. The end product of this project will be novel candidate molecules, which we will develop into new anti-B. anthracis antibiotics in our future work.